Last Updated: 27/05/2025
Novel DC targeted adenovirus vector for malaria vaccine development
Objectives
The hypothesis of this project is that a tropism-modified adenovirus vector expressing a Plasmodium multi-stage chimeric antigen will improve the quality and longevity of the immune response.
Therefore the specific aims are:
- Construct a specific camelid-derived single domain antibody moieties (sdAb) myeloid DC-targeted Ab encoding a multi-stage P. vivax chimeric antigen and validate cell-specific gene delivery using murine DCs; and
- Characterize and compare the impact of dendritic cells (DC) targeting on the immunogenicity and efficacy in a stringent murine malaria model of protection.
Malaria is the most relevant parasitic disease that continues to have a significant global impact. Given the mortality burden associated with Plasmodium falciparum, malaria research efforts have been mainly devoted to the study of this parasite. However, among the five species of malaria parasites that affect humans, P. vivax is the most widely distributed and is responsible for 50% of the clinical cases outside Africa. Clinical and epidemiological evidence also indicate that vivax malaria can also be associated with severe disease and fatal complications. Available malaria control measures have shown a significant impact on reducing morbidity and mortality in the past decade. Unfortunately, these measures are not effective against P. vivax relapse infections that result from the activation of undetectable dormant stages forms that can remain latent in the liver for several weeks after the primary infection. The development of novel tools to control or prevent P. vivax malaria is, therefore, a global health priority. A multi-stage prime-boost vaccine regimen has been developed based on chimeric recombinant proteins and recombinant adenovirus vectors, using a stringent rodent model for proof-of-principle studies. This proposal will build on experience producing recombinant adenovirus vectors to develop a novel vector with modified cell tropism to allow dendritic cells (DC)-specific targeting, using unique methodologies for genetic modification.
Apr 2016 — Mar 2018
$485,800
Related Resources
